Bone Response After Luteinizing Hormone-releasing Hormone Analogue and Enzalutamide +/- Zoledronic Acid in Prostate Cancer Patients With Hormone Sensitive Metastatic Bone Disease: a Prospective, Phase II, Randomized, Multicenter Study

Condition: Prostate Cancer, Bone Metastases

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03336983

Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Phase: Phase 2


  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 1. Histological diagnosis of prostate carcinoma, 2. Age > 18 years, 3. Metastatic disease documented as the presence of bone lesions on bone scan associated or not to soft tissue lesions measurable at computed tomography (CT) scan or Magnetic Resonance Imaging (MRI), 4. No previous hormone or chemotherapeutic treatments given for prostate carcinoma (patients that are receiving LHRH-A therapy for less than 4 months are admitted), 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0
  • 1, 6. Expected life expectancy ≥ 6 months, 7. Subject capable to swallow the Study's medication and to comply with the Study's requirements, 8. Signed informed consent.

Exclusion Criteria:

  • 1. Presence of active serious disease, active infection or co-comorbidity that may prevent the study enrollment make (at the discretion of the clinical Investigator), 2. Known or suspected brain metastases or active leptomeningeal dissemination, 3. History of other malignant neoplasm during the previous 5 years, different from the non-melanoma skin carcinoma, 4. Absolute Neutrophil Count (ANC) < 1.500/µL, platelet < 100.000/µL, or hemoglobin < 5,6 mmol/L (< 9 g/dL) at Screening Visit (notably: patients must not receive neither any growth factor during the previous 7 days nor any blood transfusion during the 28 days preceding the hematology sampling performed at Screening), 5. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2,5 x upper limit of normal (ULN) at Screening Visit, 6. Creatinine > 177 µmol/L (> 2 mg/dL) at Screening Visit, 7. Albumin ≤ 30 g/L (≤ 3,0 g/dL) at Screening Visit, 8. History of seizures or any other seizure-predisposed pathology; history of loss of consciousness or transitory ischaemic attack during the 12 months preceding the Screening visit, 9. Clinically significant cardiovascular disease including:
  • myocardial infarction (6 months preceding the screening)
  • uncontrolled angina (3 months preceding the screening)
  • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is ≥ 45%;
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
  • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
  • Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) at the Screening visit;
  • Bradycardia as indicated by a heart rate of < 50 beats per minute on the Screening ECG;
  • Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the Screening visit; 10. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months); 11. Major surgery within 4 weeks of enrollment (Day 1 Visit); 12. Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment (Day 1 visit); 13. Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease Prostate-specific antigen (PSA) levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within four weeks of enrollment (Day 1 visit); 14. Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.

View trial on